This project examines the physiological effects and the underlying biochemical mechanisms of action of delta opioid peptides and a related protein HIT (Hibernation Induction Trigger) in organ preservation and protection. Delta opioid peptide DADLE dramatically enhanced the hypothermic preservation of isolated rat lungs. Compared to controls using Euro-Collins solution which developed pulmonary edema and hemorrhage, the DADLE-preserved lungs showed good flow, almost normal vascular resistance and good oxygenation. In isolated rabbit heart preparation in which hearts were subjected to 18 hrs of global ischemia, a 15 min preconditioning of the heart with DADLE was found to greatly enhance the functional recovery of myocardium. We are currently investigating if this action of DADLE is mediated via any specific subtype of delta opioid receptors and examining if this tissue protective property of DADLE can be seen in the central nervous system.